Macrocyclic ketones as fragrance materials and methods for making same

Abstract

Novel macrocyclic diene ketone compounds useful as fragrance materials are described having the following general formula (I):where R1, R2, R3 and R4 are each either a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6. Novel pathways are described for synthesizing these macrocyclic diene ketones, as well as saturated and mono-unsaturated macrocyclic ketones having the following general formula (IV):where R1, R2, R3 and R4 are each independently a hydrogen atom or a C1 to C4 alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6.

What is claimed is:  
     
       1. A compound of the formula (I):                    
       wherein R 1 , R 2 , R 3  and R 4  are independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2, and b is an integer in a range from 1 to 6. 
     
     
       2. A compound according to claim  1 , wherein a is the integer 1 or 2 and b is an integer in a range from 2 to 5. 
     
     
       3. A compound according to claim  1 , wherein R 1 , R 2 , R 3 , and R 4  are independently H or CH 3 . 
     
     
       4. A method for synthesizing macrocyclic diene ketones of claim  1  comprising: 
       reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       performing an acyloin condensation of said linear bis-ester to form an α-hydroxyketone; and  
       reducing said α-hydroxyketone to form said macrocyclic diene ketone.  
     
     
       5. A method for synthesizing macrocyclic diene ketones of claim  1  comprising: 
       reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1  R 2  and R 3  are independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1  R 2  and R 3  are independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       reacting said linear bis-ester via a Dieckman cyclization pathway to form a β-ketoester; and  
       hydrolyzing and decarboxylating said β-ketoester to form said macrocyclic diene ketone.  
     
     
       6. The method of claim  5 , further comprising: 
       alkylating said β-ketoester prior to said hydrolyzing and decarboxylating step.  
     
     
       7. A method for synthesizing macrocyclic diene ketones of claim  1  comprising: 
       reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       performing an acyloin condensation of said linear bis-ester to form an α-hydroxyketone; and  
       reducing said α-hydroxyketone to form said macrocyclic diene ketone.  
     
     
       8. A method for synthesizing macrocyclic diene ketones of claim  1  comprising: 
       reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl and R 5  is the alkyl group of said trialkylorthoacetate; 
       reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester; and  
       hydrolyzing and decarboxylating said β-ketoester to form said macrocyclic diene ketone.  
     
     
       9. The method of claim  8  further comprising: 
       alkylating said β-ketoester prior to said hydrolyzing and decarboxylating step.  
     
     
       10. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2 , R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl and R 5  is the alkyl group of said trialkylorthoacetate; 
       hydrogenating said linear bis ester to form a saturated or mono-unsaturated linear bis-ester;  
       performing an acyloin condensation of said saturated or mono-unsaturated linear bis-ester to form an α-hydroxyketone; and  
       reducing said α-hydroxyketone to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       11. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl and R 5  is the alkyl group of said trialkylorthoacetate; 
       hydrogenating said linear bis-ester to form a saturated or mono-unsaturated linear bis-ester;  
       reacting said saturated or mono-unsaturated linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester; and  
       hydrolyzing and decarboxylating said β-ketoester to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       12. The method of claim  11  further comprising: 
       alkylating said β-ketoester prior to said hydrolyzing and decarboxylating step.  
     
     
       13. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       hydrogenating said linear bis-ester to form a saturated or mono-unsaturated linear bis-ester;  
       performing an acyloin condensation of said saturated or mono-unsaturated linear bis-ester to form an α-hydroxyketone; and  
       reducing said α-hydroxyketone to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       14. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):                    
       wherein R 1 , R 2  R 3 , and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       hydrogenating said linear bis-ester to form a saturated or mono-unsaturated linear bis-ester;  
       reacting said saturated or mono-unsaturated linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester; and  
       hydrolyzing and decarboxylating said β-ketoester to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       15. The method of claim  14 , further comprising: 
       alkylating said β-ketoester prior to said hydrolyzing and decarboxylating step.  
     
     
       16. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2, and b is an integer in a range from 1 to 6, comprising: 
       reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       performing an acyloin condensation of said linear bis-ester to form an α-hydroxyketone;  
       hydrogenating said α-hydroxyketone to form a saturated or mono-unsaturated α-hydroxyketone; and  
       reducing said saturated or mono-unsaturated α-hydroxyketone to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       17. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;  
       hydrogenating said β-ketoester to form a saturated or mono-unsaturated β-ketoester; and  
       hydrolyzing and decarboxylating said saturated or mono-unsaturated β-ketoester to form a saturated or mono-unsaturated macrocyclic ketone.  
     
     
       18. The method according to claim  17 , further comprising: 
       alkylating said β-ketoester prior to said hydrogenation step.  
     
     
       19. The method according to claim  17 , further comprising: 
       alkylating said saturated or mono-unsaturated β-ketoester prior to said hydrolyzing and decarboxylating step.  
     
     
       20. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       performing an acyloin condensation of said linear bis-ester to form an α-hydroxyketone;  
       hydrogenating said α-hydroxyketone to form a saturated or mono-unsaturated α-hydroxyketone; and  
       reducing said saturated or mono-unsaturated α-hydroxyketone to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       21. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;  
       hydrogenating said β-ketoester to form a saturated or mono-unsaturated β-ketoester; and  
       hydrolyzing and decarboxylating said saturated or mono-unsaturated β-ketoester to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       22. The method of claim  21 , further comprising: 
       alkylating said β-ketoester prior to said hydrogenation step.  
     
     
       23. The method of claim  21 , further comprising: 
       alkylating said saturated or mono-unsaturated β-ketoester prior to said hydrolyzing and decarboxylating step.  
     
     
       24. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       performing an acyloin condensation of said linear bis-ester to form an α-hydroxyketone;  
       reducing said α-hydroxyketone to form a macrocyclic diene ketone; and  
       hydrogenating said macrocyclic diene ketone to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       25. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting an optionally substituted 1,ω-dialdehyde with a Grignard reagent to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;  
       hydrolyzing and decarboxylating said β-ketoester to form a macrocyclic diene ketone; and  
       hydrogenating said macrocyclic diene ketone to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       26. The method of claim  25 , further comprising: 
       alkylating said β-ketoester prior to said hydrolyzing and decarboxylating step.  
     
     
       27. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester having the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       performing an acyloin condensation of said linear bis-ester to form a α-hydroxyketone;  
       reducing said α-hydroxyketone to form a macrocyclic diene ketone; and  
       hydrogenating said macrocyclic diene ketone to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       28. A method for synthesizing saturated or mono-unsaturated macrocyclic ketones having the following general formula (IV):                    
       wherein R 1 , R 2 , R 3  and R 4  are each independently a hydrogen atom or a C 1  to C 4  alkyl, a is the integer 1 or 2 and b is an integer in a range from 1 to 6, comprising: 
       reacting a 1,ω-di-Grignard reagent with an unsaturated aldehyde to form a bis-allyl alcohol of the following general formula (II):                    
       wherein b is an integer in a range from 1 to 6 and R 1 , R 2  and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl; 
       reacting said bis-allyl alcohol with a trialkylorthoacetate in the presence of acid catalysis resulting in a bis-Claisen rearrangement to form a linear bis-ester of the following general formula (III):                    
       wherein b is an integer in a range from 1 to 6, R 1 , R 2 , and R 3  are each independently a hydrogen atom or a C 1  to C 4  alkyl, and R 5  is the alkyl group of said trialkylorthoacetate; 
       reacting said linear bis-ester via a Dieckmann cyclization pathway to form a β-ketoester;  
       hydrolyzing and decarboxylating said β-ketoester to form a macrocyclic diene ketone; and  
       hydrogenating said macrocyclic diene ketone to form said saturated or mono-unsaturated macrocyclic ketone.  
     
     
       29. The method of claim  28 , further comprising: 
       alkylating said β-ketoester prior to said hydrolyzing and decarboxylating step.  
     
     
       30. A fragrance composition comprising a compound of claim  1  in combination with at least one of a carrier and additional perfumery material. 
     
     
       31. A fragrance composition according to claim  30 , further comprising a surfactant to form a product, whereby said product is effective to act as at least one of a cleaning agent, a skin cream, a hand and body lotion, a sunscreen agent, a hair conditioner, a water-based adhesive, a water-based paint, a shampoo, a dish washing liquid, a heavy duty cleaner, a general purpose cleaner, a liquid abrasive cleaner, a liquid soap, a laundry detergent, a deodorant, an antiperspirant, a bleach, an air care product and a fabric softener. 
     
     
       32. A fragrance composition comprising a compound of claim  2  in combination with at least one of a carrier and additional perfumery material. 
     
     
       33. A fragrance composition according to claim  32 , further comprising a surfactant to form a product, whereby said product is effective to act as at least one of a cleaning agent, a skin cream, a hand and body lotion, a sunscreen agent, a hair conditioner, a water-based adhesive, a water-based paint, a shampoo, a dish washing liquid, a heavy duty cleaner, a general purpose cleaner, a liquid abrasive cleaner, a liquid soap, a laundry detergent, a deodorant, an antiperspirant, a bleach, an air care product and a fabric softener. 
     
     
       34. A fragrance composition comprising a compound of claim  3  in combination with at least one of a carrier and additional perfumery material. 
     
     
       35. A fragrance composition according to claim  34 , further comprising a surfactant to form a product, whereby said product is effective to act as at least one of a cleaning agent, a skin cream, a hand and body lotion, a sunscreen agent, a hair conditioner, a water-based adhesive, a water-based paint, a shampoo, a dish washing liquid, a heavy duty cleaner, a general purpose cleaner, a liquid abrasive cleaner, a liquid soap, a laundry detergent, a deodorant, an antiperspirant, a bleach, an air care product and a fabric softener.